Yaz, Yasmin & Ocella

In the “Medication Update” section of a 2011 edition of the medical journal The Nurse Practitioner, a warning regarding the use of drospirenone-containing oral contraceptives is made. Oral contraceptives containing drospirenone are YAZ®, Beyaz®, Safyal®, and Yazmin®.

The warning reads as follows:

“The FDA notified healthcare providers and patients that two newly published studies evaluating the risk of [blood clot development] in women who use oral contraceptives (OCs) containing the progestin drospirenone found a greater risk of [blood clot] associated with drospirenone-containing OCs compared with OCs that contain levonorgestrel.”[1]

That increased risk of developing a blood clot was stated to be “two or three times greater … in women taking drospirenone-containing OCs than was seen among women taking levonorgestrel-containing OCs.”[2]

The development of a blood clot can be a very serious medical event. If a blood clot becomes lodged in the brain, one can have a stroke, and if a blood clot becomes lodged in the heart, one may have a heart attack.

A lawyer may cite this article in a Yaz lawsuit to demonstrate that the medical community has been aware of the increased risk of adverse health effects posed to users of oral contraceptives such as YAZ®, and that users of this and other such drugs are placed at higher risk without any potential higher reward: drospirenone-containing oral contraceptives are no more effective than those that do not contain drospirenone.

A 2010 report by the medical journal Reactions describes the case of a 20-year-old woman, otherwise in good health, who suffered a heart attack while taking an oral contraceptive containing the chemical drospirenone, found in contraceptives such as YAZ®.

The case of this woman, holding no risk factors for blood clot or heart attack other than the consumption of drospirenone-containing oral contraceptives, warranted the following comment from the author: “We consider that the use of the contraceptive pill contributed significantly to the thromboembolic event described here.”[1] (Thromboembolic event means blood clot.) Thankfully, the woman recovered.[2]

Though this article does not provide explicit biological evidence of how drospirenone-containing contraceptives produce increased risk to users of blood clot, this publication may be used by a Yaz lawyer to illustrate one simple case of the undue dangers drospirenone use may pose.

An article published in 2009 in the British Medical Journal by Dr. A. van Hylckama Vlieg (et al.) analyzes the risk of developing a blood clot for women using hormonal contraceptives (versus non-users) and evaluates the relative risk for developing a blood clot between different types of hormonal contraceptives used today, naming the active chemical in the drug commonly known as YAZ® as significantly more dangerous than the average hormonal contraceptive.

For this study, Vlieg surveyed 1524 women who had developed blood clots regarding their use of hormonal contraceptives, and found that 72.4% were using such contraceptives at the time of the clot.[1] And through statistical analysis, the study establishes that “overall, current oral contraceptive use was associated with a fivefold increased risk of venous thrombosis”[2] (Venous thrombosis is the instance of a blood clot.)

Among different oral contraceptives, however, health risks are not equal. Evaluating the rate of venous thrombosis among users of many oral contraceptives commonly used today, Vlieg found that users of contraceptives containing drospirenone (such as YAZ®) are placed at a 70% greater risk of venous thrombosis than the average oral contraceptive user, and 630% more likely to develop a blood clot than is a non-user.[3]

A lawyer can use this article in a Yaz lawsuit to demonstrate that drugs such as YAZ® pose an unnecessarily high risk of venous thrombosis to users, considering that there is no observed increase in drug efficacy to theoretically justify the risk.

The “Drug Watch” section of the September, 2012 edition of the American Journal of Nursing includes some startling information about hormonal contraceptive drugs containing the chemical drospirenone, such as YAZ,® Beyaz®, Safyral®, and Yasmin®.

Reviewing several studies comparing the relative risks of developing a blood clot for women using drospirenone-containing hormonal contraceptives versus women using other hormonal contraceptives, including one funded by the FDA itself, the American Journal of Nursing writes, “the FDA has concluded that there is an increased risk of blood clots if the contraceptive drospirenone; the increased risk may be as much as three times higher.”[1] (emphasis added)

Blood clots can be very dangerous, possibly resulting in stroke or heart attack. Thankfully, the article goes on to note that these drugs now contain such warnings on their packaging,[2] but I ask, why use any drug that has been found to be more dangerous than others with no significant increase in efficacy?

Articles such as this can be used in a pharmaceutical lawsuit by a Yaz lawyer to demonstrate that it is now common knowledge in the scientific community that drugs containing drospirenone place users at a higher risk for blood clots than do other oral contraceptives – in some cases three times the risk.

A study published in May, 2009 by the British Medical Journal notes that women using hormonal contraceptives containing drospirenone, such as Yaz®, are about 64% more likely to develop blood clots than the average woman using hormonal contraceptives.[1] Blood clots pose a very serious risk to health, as they may cause heart attack or stroke.

For the study, titled “Hormonal contraception and risk of venous thromboembolism: national follow-up study” by Lidegaard et al. surveyed the health of 10.4 million women, and found that in the general population, the risk for developing blood clots was about 3 out of every 10,000 women,[2] while the risk for women using hormonal contraceptives was about double that, at 6.29 out of 10,000 women.[3] But the Lidegaard team did not stop their research at that discovery; the study went on to evaluate the relative risk of developing blood clots for different kinds of hormonal contraceptives.

Compared to the average risk of developing blood clots posed by the ingestion of hormonal contraceptives, the study found that medications containing desogrestrel place women about 82% more likely to develop blood clots than the average user of hormonal contraceptives, gestodene about 86% more likely, cyproterone about 88% more likely, and drospirenone about 64% more likely than the average hormonal contraceptive user to develop blood clots.[4]

However, concerning what was considered the “crude rate” of blood clot development, calculated simply by dividing the number of blood clots observed by the number of woman-years for each particular pharmaceutical discussed in the study, drospirenone (YAZ®) was found to be the most dangerous, averaging 7.8 observed blood clots per 10,000 users. This stood above all other hormonal contraceptives tested, with norethisterone at 4.5, levonorgestrel at 5.8, norgestimate at 4.6, desogestrel at 6.5, gestodene at 7.0, and cyproterone at 7.1 observed blood clots per 10,000 women.

Because of the startling information presented here, this article can be used in a Yaz lawsuit, demonstrating that the risks of YAZ® are much higher than the average hormonal contraceptive.

A report published in 2006 in the medical journal Clinical and Applied Thombosis/Hemostasis reviews the case of a woman, aged 36 years, who came under the care of Dr. Y. Mira, presenting deep venous thromboses (blood clots) in the “left jugular and subclavian” veins.[1] Blood clots are a very serious occurrence, possibly leading to heart attack or stroke.

Because the patient had no family history of blood clotting,[2] and demonstrated no other risk factors, doctors concluded that the patient’s use of “Yazmin®,” a hormonal contraceptive containing drospirenone, known to place its users at a higher risk for the development of blood clots than other hormonal contraceptives, “was the only associated risk factor…,”[3] and likely caused the event.

Other oral contraceptives that contain drospirenone, and thus place women at a higher risk for blood clots, are YAZ®, Beyaz®, and Safyral®.

While this article did not describe in detail the biochemistry of how drospirenone causes blood clots, from it we learn that this chemical is known by the medical research community to be more dangerous than its “peer” chemicals, if you will, though it does not demonstrate increased efficacy in pregnancy prevention. As such, Dr. Mira’s piece may be used by in a Yaz lawsuit to help provide evidence that the drugs Yaz®, Beyaz®, Safyal®, and Yazmin®, each place users at an unnecessarily high risk for serious adverse health effects.

For those of us less aware of hyperkalemia, Bird writes that “Hyperkalemia is a potentially serious condition … manifesting as weakness, flaccid paralysis, hypoventilation, and metabolic acidosis. Hyperkalemia can also result in cardiac toxicity with electrocardiographic changes, which in severe cases may lead to the terminal events of ventricular fibrillation or asystole.”[2] (emphasis added)

Here is how MedlinePlus, a service of the U.S. National Library of Medicine, and the National Institutes of Health, describes the ailments Dr. Bird writes can result from hyperkalemia:

Flaccid Paralysis: “paralysis in which muscle tone is lacking in the affected muscles and in which tendon reflexes are decreased or absent.”[3]

Hypoventilation: “deficient ventilation of the lungs that results in reduction in the oxygen content or an increase in carbon dioxide of the blood or both.”[4] This is bad – all of your organs need oxygen to function.

Metabolic Acidosis: “Acidosis resulting from excess acid due to abnormal metabolism, excessive acid intake, or renal retention or from excessive loss of bicarbonate (as in diarrhea).”[5]

Acidosis: “An abnormal condition of reduced alkalinity of the blood and tissues that is marked by sickly sweet breath, headache, nausea and vomiting, and visual disturbances and is usually a result of excessive acid production.”[6]

Ventricular Fibrillation: “Very rapid uncoordinated fluttering contractions of the ventricles of the heart resulting in loss of synchronization between heartbeat and pulse beat.”[7]

Systole: “The contraction of the heart by which the blood is forced onward and the circulation kept up.”[9]

The Bird (et al.) results, though deemed not clinically significant due to the sample size, suggest danger of YAZ® use and ought to prompt further study on this subject. A Yaz lawyer can use this article in a Yaz, Yazmin, or Ocella lawsuit to help provide evidence that YAZ® poses excessive and unjustified risk to its users.

[3] “Flaccid Paralysis” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/flaccid%20paralysis> Accessed 4 October 2012

[4] “Hypoventilation” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/hypoventilation> Accessed 4 October 2012

[5] “Metabolic Acidosis” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/Metabolic%20Acidosis> Accessed 4 October 2012

[6] “Acidosis” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/acidosis> Accessed 4 October 2012

[7] “Ventricular Fibrillation” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/ventricular%20fibrillation> Accessed 4 October 2012

[8] “Asystole” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/asystole> Accessed 4 October 2012

[9] “Systole” MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. Available at <http://www.merriam-webster.com/medlineplus/systole> Accessed 4 October 2012

This Yasmine lawsuit was filed in March of 2009 in the Northern District of California:

21. Yasmin, known generically as drospirenone and ethinyl estradiol, is a combination birth control pill containing the hormones estrogen and progestin and was approved by the FDA in April 2001. In the case of Yasmin, the estrogen is ethinyl estradiol and the progestin is drospirenone.

22. Yasmin is indicated for the prevention of pregnancy in women who elect to use an oral contraceptive.

23. Combination birth control pills are referred to as combined hormonal oral contraceptives.

24. The difference between Yasmin and other birth control pills on the market is that drospirenone has never before been marketed in the United States and is unlike other progestins available in the United States.

25. In April 2002, the British Medical Journal reported that the Dutch College of General Practitioners recommended that older second generation birth control pills be prescribed in lieu of Yasmin as a result of 40 cases of venous thrombosis among women taking Yasmin.

26. In February 2003, a paper entitled Thromboembolism associated with the newly contraceptive Yasmin was published in the British Medical Journal detailing a Netherlands Pharmacovigilance Centre report of five additional reports of thromboembolism where Yasmin was suspected as the cause, including two deaths.

27. Defendants have twice been warned by the FDA, in 2003 and 2008, for misleading the public through the use of television ads which overstate the efficacy of Yasmin and minimize serious risks associated with the drug.

28. The use of Yasmin has a prothrombotic effect resulting in thrombosis such as the pulmonary embolism suffered by Plaintiff.

29. Defendants failed or neglected to recognize the correlation between the use of Yasmin and increased thrombosis formation despite the wealth of scientific information available.

30. Upon information and belief, Defendants knew or should have known about the correlation between Yasmin use and a prothrombotic effect and still promoted, sold, advertised, and marketed the use of Yasmin.

31. As a result of the manufacture, marketing, advertising, promotion, distribution and/or sale of Yasmin to Plaintiff herein, Plaintiff was prescribed with and ingested Yasmin, sustaining severe and permanent personal injuries, to wit: pulmonary embolism and all resulting damages, including the potential for future thrombembolic events.

15. YASMIN received FDA approval first in 2001. It is a combination of drospirenone, a progestin, and ethinyl estradiol, an estrogen.

16. YAZ received approval from the FDA in 2006 and is essentially the same as YASMIN, with the only difference being a slightly smaller amount of ethinyl estradiol.

17. YAZ and YASMIN are indicated for the prevention of pregnancy in women who elect to use an oral contraceptive.

18. Combination birth control pills are referred to as combined hormonal oral contraceptives.

19. The difference between YAZ and other birth control pills on the market is that drospirenone has never before been marketed in the United States and is unlike other progestins available in the United States.

20. In April 2002, the British Medical Journal reported that the Dutch College of General Practitioners recommended that older second generation birth control pills be prescribed in lieu of YASMIN as a result of 40 cases of venous thrombosis among women taking YAZ/YASMIN.

21. In February 2003, a paper entitled Thromboembolism associated with the new contraceptive YAZ/YASMIN was published in the British Medical Journal detailing a Netherlands Pharmacovigilance Centre report of additional reports of thromboembolism where YAZ/YASMIN was suspected as the cause, including two deaths.

22. Defendants have twice been warned by the FDA, in 2003 and 2008, for misleading the public through the use of television advertisements which overstate the efficacy of the drugs and minimize the serious risks associated with the drugs.

23. The use of YAZ/YASMIN has a prothrombotic effect resulting in the development of thromboses, such as pulmonary emboli and deep vein thrombosis.

24. Defendants failed to recognize the correlation between the use of YAZ/YASMIN and increased thrombosis formation despite the wealth of scientific information available.

25. Upon information and belief, Defendants knew or should have known about the correlation between YAZ/YASMIN use and a prothrombotic effect and still promoted, sold, advertised, and marketed the use of YAZ/YASMIN without sufficient warnings.

26. YAZ/YASMIN use of drospirenone, a diuretic, creates unique risks for compared to other oral contraceptives. These risks include heart arrhythmias, myocardial infarction, and other adverse cardiovascular events, including sudden death.

27. The diuretic in YAZ/YASMIN is also known to cause problems with the gallbladder; the problems sometimes require surgical intervention. The diuretic also causes kidney stone formation.

The following Yaz lawsuit was filed in August of 2008 in the U.S. District Court for the Southern District of Illinois:

13. Yaz and Yasmin are birth control pills manufactured and marketed by
Defendants. They are combination oral contraceptives, or “COCs,” meaning that they
contain an estrogen component and a progestin component. Together, these steroidal
components work together in COCs to suppress ovulation, fertilization, and implantation and thus prevent pregnancy.

14. Yaz and Yasmin were approved by the Food and Drug Administration for marketing
in 2006 and 2001, respectively.

15. The estrogen component in Yaz/ Yasmin is known generically as ethinyl estradiol. The progestin component is known as drospirenone. Yasmin contains 0.03 milligrams of ethinyl estradiol, and Yaz contains 0.02 milligrams of ethinyl estradiol. Both products contain 3 milligrams of drospirenone.

16. Yaz and Yasmin are different from other combined hormonal birth control pills in that they contain drospirenone, a progestin that is unlike other progestins available in the United States and was never before marketed in the United States prior to its use in Yaz/ Yasmin.

17. Shortly after the introduction of combined oral contraceptives in the 1960’s, doctors and researchers found that women using birth control pills had a higher risk of blood clots, heart attacks, and strokes than women not using the pill. As a result, the various brands of birth control pills were reformulated to reduce the amounts of estrogen. As the amounts of estrogen levels reduced, so too did the risk of blood clots, heart attacks, and strokes.

18. During this time, new progestins were being developed, which became known as
“second generation” progestins (e.g. lovenorgestrel). These second generation progestins, when combined with the lower amounts of the estrogen, ethinyl estradiol, helped to reduce the risk of blood clots, heart attacks, and strokes and were considered safer for women.

19. During the 1990’s, new “third generation” progestins were developed. Unfortunately, these “third generation” progestins (e.g. gestodene and desogestrel) have been associated with a greater risk of blood clots in the deep veins (deep vein thrombosis or “DVT”) and lungs (Pulmonary Embolismsm or “PE”). As a result of this increased risk of blood clots, the FDA has required that products containing third generation progestins include a Warning of the potentially increased risk of thrombosis.

20. Yaz and Yasmin contain the same estrogen component, ethinyl estradiol which has been used in the lower dose birth control pills for decades.

21. However, drospirenone is a new type of progestin and is considered a “fourth generation” progestin. No other birth control pills contain drospirenone, except for a recently approved generic version of Yaz/ Yasmin marketed under the trade name Ocella.

22. Since drospirenone is new, there is insufficient data available to support its safe use, particularly compared with second generation progestins. In fact, studies performed prior to FDA approval indicate that drospirenone has certain effects that are different from those of traditional second generation progestins, and potentially more dangerous.

23. One possible mechanism of action is that drospirenone causes an increase in potassium levels in the blood, which can lead to a condition known as hyperkalemia if the potassium levels become too high. Hyperkalemia can cause heart rhythm disturbances, such as extrasystolies, pauses, or bradycardia. If left untreated, hyperkalemia can be fatal. If hyperkalemia disrupts the normal heart rhythms, the flow of blood through the heart can be slowed to the point that it permits blood clots to form. Blood clots in the heart can then lead to heart attacks, or the clots can break off and travel to the lungs where they can cause a pulmonary embolism, or can travel to the brain causing stroke.

24. During the brief time that Yaz/ Yasmin have been sold in the United States, hundreds of reports of injury and death have been submitted to the FDA in association with defendants’ products.

25. In April 2002, the British Medical Journal reported that the Dutch College of General Practitioners recommended that older second generation birth control pills be prescribed in lieu of Yasmin as a result of 40 cases of venous thrombosis among women taking Yasmin.

26. In February 2003, a paper entitled ThromboEmbolismsm Associated with the New contraceptive Yasmin was published in the British Medical Journal detailing a Netherlands Pharmacovigilance Centre report of five additional reports of thrombo Embolismsm where Yasmin was suspected as the cause, including two deaths.

27. In fact, in less than a five-year period, from the first quarter of 2004 through the third quarter of 2008, over 50 reports of death among users of Yaz / Yasmin have been filed with the FDA.

28. These reports include deaths associated with cardiac arrhythmia, cardiac arrest, intracardiac thrombus, heart attack, and stroke in women in their child bearing years.

29. Some deaths reported occurred in women as young as 17 years old.

30. Significantly, reports of elevated potassium levels are frequently included among the symptoms of those suffering death while using Yaz/ Yasmin.

About this Blog

This blog chronicles legal and scientific news relating to personal injuries caused by defective drugs and medical devices. It is published by injury lawyer Justinian C. Lane, an attorney who takes a personal interest in each of his clients’ cases.